Douglas S Goodin1, Anthony T Reder2, Anthony L Traboulsee3, David Kb Li3, Dawn Langdon4, Gary Cutter5, Stuart Cook6, Timothy O'Donnell7, Marcelo Kremenchutzky8, Joel Oger9, Ralf Koelbach10, Christoph Pohl11, Eva-Maria Wicklein12. 1. Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. 2. Department of Neurology, The University of Chicago, Chicago, IL, USA. 3. The University of British Columbia, Vancouver, BC, Canada. 4. Department of Psychology, Royal Holloway, University of London, London, UK. 5. Department of Biostatistics, UAB School of Public Health, Birmingham, AL, USA. 6. Department of Neurosciences, Rutgers University, Newark, NJ, USA. 7. Pompton Lakes Pulmonary P.C., Lincoln Park, NJ, USA. 8. Western University and London Health Sciences Centre, London, ON, Canada. 9. Department of Neurology, The University of British Columbia, Vancouver, BC, Canada. 10. PAREXEL International, Berlin, Germany. 11. Bayer AG, Berlin, Germany; University Hospital Bonn, Bonn, Germany. 12. Bayer AG, Berlin, Germany.
Abstract
BACKGROUND: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). OBJECTIVE: To examine the predictive validity of different NEDA definitions. METHODS:Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed. NEDA in the first 2 years was defined as follows: clinical NEDA: no relapses or Expanded Disability Status Scale (EDSS) progression from baseline to Year 2; NEDA-3a: no relapses, no confirmed ⩾1-point EDSS progression, and no new T2-active lesions; NEDA-3b: no relapses, no EDSS progression, and no increase in T2 burden of disease (T2-BOD); and NEDA-4: no relapses, no EDSS progression, and no increase in T2-BOD or atrophy. NDOs were defined as death, need for wheelchair, EDSS ⩾6, or progressive MS. RESULTS:A total of 245 and 371 patients were evaluated at 16 and 21 years, respectively. Clinical NEDA predicted NDOs ( p = 0.0029), as did baseline EDSS ( p < 0.0001), baseline T2-BOD ( p < 0.0001), and change in T2-BOD ( p = 0.0033). IFNB-1b treatment ( p = 0.0251), relapse rate in the 2 years before study start ( p = 0.0260), T2-BOD at baseline ( p = 0.0014), and change in T2-BOD ( p = 0.0129) predicted survival at 21 years. CONCLUSION:Clinical NEDA predicted long-term disability outcome. By contrast, definitions of NEDA that included on-therapy changes in magnetic resonance imaging variables did not increase the predictive validity.
RCT Entities:
BACKGROUND: Long-term follow-up from the randomized trial of interferon beta-1b (IFNB-1b) permitted the assessment of different definitions of no evidence of disease activity (NEDA) for predicting long-term outcome in multiple sclerosis (MS). OBJECTIVE: To examine the predictive validity of different NEDA definitions. METHODS: Predictive validity for negative disability outcomes (NDOs) at 16 years and survival at 21 years post-randomization were assessed. NEDA in the first 2 years was defined as follows: clinical NEDA: no relapses or Expanded Disability Status Scale (EDSS) progression from baseline to Year 2; NEDA-3a: no relapses, no confirmed ⩾1-point EDSS progression, and no new T2-active lesions; NEDA-3b: no relapses, no EDSS progression, and no increase in T2 burden of disease (T2-BOD); and NEDA-4: no relapses, no EDSS progression, and no increase in T2-BOD or atrophy. NDOs were defined as death, need for wheelchair, EDSS ⩾6, or progressive MS. RESULTS: A total of 245 and 371 patients were evaluated at 16 and 21 years, respectively. Clinical NEDA predicted NDOs ( p = 0.0029), as did baseline EDSS ( p < 0.0001), baseline T2-BOD ( p < 0.0001), and change in T2-BOD ( p = 0.0033). IFNB-1b treatment ( p = 0.0251), relapse rate in the 2 years before study start ( p = 0.0260), T2-BOD at baseline ( p = 0.0014), and change in T2-BOD ( p = 0.0129) predicted survival at 21 years. CONCLUSION: Clinical NEDA predicted long-term disability outcome. By contrast, definitions of NEDA that included on-therapy changes in magnetic resonance imaging variables did not increase the predictive validity.
Authors: Thomas F Scott; Ray Su; Kuangnan Xiong; Arman Altincatal; Carmen Castrillo-Viguera; Maria L Naylor Journal: Ther Adv Neurol Disord Date: 2021-01-12 Impact factor: 6.570
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